HomeMCPWorkbenchSkills
HomeWorkbenchNotificationsMe
llms.txt · MCP GuidePrivacy Policy · Terms of Service · Supportv1.8.0
  1. Home
  2. /Reaction

275387-85-4 → (Z)-4-[(3R,4R)-3-Amino-4-hydroxy-1-pentynyl]-1,3-dihydro-5-fluoro-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one

HRID 366735
Notes
Print preview

Reaction equation

HRID 366735 reaction equation
C([N:8]1[C@H:12]([C:13]#[CH:14])[C@@H:11]([CH3:15])[O:10]C1(C)C)(OC(C)(C)C)=O.[F:18][C:19]1[C:20](I)=[C:21]2[C:25](=[CH:26][CH:27]=1)[NH:24][C:23](=[O:28])/[C:22]/2=[CH:29]\[C:30]1[NH:31][CH:32]=[CH:33][C:34]=1[O:35][CH3:36].FC(F)(F)C(O)=O.C(Cl)Cl>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN(C=O)C.CCN(CC)CC.C(Cl)Cl.O>[NH2:8][C@@H:12]([C@H:11]([OH:10])[CH3:15])[C:13]#[C:14][C:20]1[C:19]([F:18])=[CH:27][CH:26]=[C:25]2[C:21]=1/[C:22](=[CH:29]/[C:30]1[NH:31][CH:32]=[CH:33][C:34]=1[O:35][CH3:36])/[C:23](=[O:28])[NH:24]2
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

9

Reactant 3

HCID 12970128275387-85-4HCID 18363902(3Z)-5-fluoro-4-iodo-3-[(3-methoxy-1H-pyrrol-2-yl)methylidene]-2,3-dihydro-1H-indol-2-one2×HCID 21863450Trifluoroacetic acid methylene chloride

Product 1

HCID 23645079(Z)-4-[(3R,4R)-3-Amino-4-hydroxy-1-pentynyl]-1,3-dihydro-5-fluoro-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one

Reagents, catalysts & solvents 5

HCID 962
Water
Catalyst
HCID 178418397HCID 178418397, compoundCatalyst
HCID 6228DimethylformamideSolvent
HCID 6344DichloromethaneSolvent
HCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

Using Method C above, (4R,5R)-N-Boc-2,2,5-trimethyl-4-ethynyl-oxazolidine (0.18 g, 0.65 mmol) (Example 102B) was coupled with (Z)-1,3-dihydro-5-fluoro-4-iodo-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one (0.1 g, 0.26 mmol) (Starting Material 6) using (Ph3P)4Pd (30 mg) and Cul (6 mg) as catalyst in DMF (6 mL) and Et3N (6 mL) as solvent at 85° C. for 1 day. To the resulting compound in CH2Cl2 (6 mL) was added a 1:1 mixture of trifluoroacetic acid/CH2Cl2 (6 mL) and 3 drops of water at 0° C. and the mixture was stirred at 0° C. for 1.5 h. The mixture was then quenched with conc. NH4OH (6 mL) and diluted with EtOAc. The organic layer was washed with brine and dried with MgSO4. (Z)-4-[(3R,4R)-3-Amino-4-hydroxy-1-pentynyl]-1,3-dihydro-5-fluoro-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one was purified via flash column chromatography (10% MeOH in CH2Cl2). (Yield 44 mg, 48%).

Workup

  1. customThe mixture was then quenched with conc. NH4OH (6 mL)
  2. additiondiluted with EtOAc
  3. washThe organic layer was washed with brine
  4. dry with materialdried with MgSO4
  5. custom(Z)-4-[(3R,4R)-3-Amino-4-hydroxy-1-pentynyl]-1,3-dihydro-5-fluoro-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one was purified via flash column chromatography (10% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-0f79e60258df40cca51f40ecc489c8a0
Source dataset
uspto-grants-2000_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06130239

Reaction notes

Loading…

On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes